Introduction

Fractional flow reserve (FFR) is a reliable and validated method for assessing the hemodynamic significance of a coronary stenosis during angiography. An FFR-guided strategy, wherein percutaneous coronary intervention (PCI) is deferred when the FFR ≥0.75-0.8 has been shown to improve patient outcomes and is endorsed by the current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. Though deferral of FFR-guided non-significant lesions is considered safe, the rates of deferred lesion intervention (DLI) are highly variable depending on the clinical characteristics, technical aspects, and FFR cutoff values utilized in individual studies. This observational study was designed to assess the clinical predictors of DLI in a relatively large single-center cohort.

Methods

This was a retrospective cohort study involving 721 patients with 882 coronary lesions, in whom revascularization was deferred based on FFR between 2002 and 2010. Any subsequent revascularization of these lesions, including PCI and coronary artery bypass grafting (CABG), was defined as DLI. Risk prediction models for DLI were developed using stepwise Cox regression modeling and were internally validated.

Results

The mean age of the study population was 64.5 years. At the time of FFR, approximately half of the patients had acute coronary syndrome (ACS) and 27% underwent PCI of other lesions. FFR was >0.80 in 93% of lesions, and 0.75-0.80 in 7% of lesions. Proximal left coronary arteries were involved in 34% of all deferred lesions. Medical therapy was similar in patients who did and did not undergo DLI. During a mean follow-up period of 4.0 + 2.3 years, 17% of patients died, 11% had an MI, and DLI was performed in 18% (155) lesions (74% by PCI and 26% by CABG). The rates of DLI and acute myocardial infarction (AMI) were 5.3% and 0.8% at the end of first year. The indications for DLI were AMI (19%), unstable angina (46%) and elective revascularization for stable angina (34%). Using the six independent predictors of DLI (age, creatinine, multivessel coronary artery disease (CAD), FFR value, history of current/former smoking, CAD, or prior PCI), an algorithm was designed to predict the one-year risk of DLI in each deferred lesion.

Conclusion

In patients with deferred coronary lesions based on FFR, the risk of DLI was about 5% in the first year and 18% at four years. A clinical prediction tool based on five clinical factors and FFR value can estimate the risk of DLI and help guide treatment decisions.

Commentary/Perspective

The limitations of coronary angiography in estimating lesion severity and the incremental benefits of FFR in patients with intermediate coronary stenoses are well-established. FFR- guided intervention (<0.75-0.8) and deferral (≥0.75-0.8) has been shown to improve patient outcomes as well as decrease health care costs. However, between 2.5 and 11% of patients in whom PCI is deferred based on FFR have recurrent cardiac events necessitating subsequent revascularization. This study provides two key findings. First, it confirms that the rates of DLI, MI, and mortality are relatively low even in a high-risk group of patients (>50% ACS and 12% AMI) in whom PCI is deferred based on FFR. Second, it provides a model for predicting one-year rates of DLI based on simple characteristics available at the time of index FFR measurement. The risk prediction model is based on six independent predictors of risk of DLI identified in this cohort: younger age, chronic kidney disease, prior or current smoking, prior CAD, multivessel disease, and FFR value. This is a single-center study, and the findings require external validation. More importantly, it is unknown whether patients categorized as high risk for DLI and who have an FFR of 0.8-0.85 will have better outcomes with PCI at the time of index cardiac catheterization. However, if these questions are answered with future studies, the use of this risk model in conjunction with FFR may lead to improved patient outcomes.